title: DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats.
abstract: The purpose of this study was to determine whether administration of dehydroepiandrosterone (DHEA) protects male rats against the accumulation of body fat the development of insulin resistance with advancing age. We found that supplementation of the diet with 0.3% DHEA between the ages of 5 months and approximately 25 months resulted in a significantly lower final body weight (DHEA, 593 +/- 18 g vs control, 668 +/- 12 g, p < 0.02), despite no decrease in food intake. Lean body mass was unaffected by the DHEA, and the lower body weight was due to a approximately 25% reduction in body fat. The rate of glucose disposal during a euglycemic, hyperinsulinemic clamp was 30% higher in the DHEA group than in the sedentary controls due to a greater insulin responsiveness. The DHEA administration was as effective in reducing body fat content and maintaining insulin responsiveness as exercise in the form of voluntary wheel running. The DHEA had no significant effect on muscle GLUT4 content. A preliminary experiment provided evidence suggesting that muscle insulin signaling, as reflected in binding of phosphatidylinositol 3-kinase to the insulin receptor substrate-1, was enhanced in the DHEA-treated and wheel running groups as compared to controls. These results provide evidence that DHEA, like exercise, protects against excess fat accumulation and development of insulin resistance in rats.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Han
authors.forename: P A
authors.initials: PA
authors.lastname: Hansen
authors.forename: M M
authors.initials: MM
authors.lastname: Chen
authors.forename: J O
authors.initials: JO
authors.lastname: Holloszy
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000375:Aging; D000818:Animals; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D004435:Eating; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C495694:Slc2a4 protein, rat; D003687:Dehydroepiandrosterone; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose